Patient Medicine and Social Genoming

Following his neurologist’s advice, for 14 years a multiple sclerosis patient took a daily 10-milligram pill to mitigate the effects of “foot drop.” It didn’t work all that well, but the neurologist said a higher dose would be deleterious. Last year, on a website called PatientsLikeMe, the patient discovered nearly 200 patients like him who were routinely taking up to 80 milligrams of the same drug, and doing just fine. He got his neurologist to up his dosage to 40 milligrams, and his foot drop improved significantly.

PatientsLikeMe is a website where some 7,000 (as of March 2008) patients share hard data about their demographics and symptoms and drugs and dosages and outcomes. Neatly graphed and tabulated on the website, these data enable patients to manage their disease “with a sophistication and precision that would have been unimaginable just a decade ago,” as Thomas Goetz put it in the New York Times Magazine (March 23), but it “raises a host of questions for medicine,” such as what happens to the role of doctors, what dangers to patients does it bring, what if it contradicts findings from formal clinical research, and what if (as seems to be the case) it encourages patients to do their own clinical trials of untested drugs and therapies?

A PatientsLikeMe founder told Goetz that the company can now use the data to model each patient mathematically and then tell patients “what’s going to happen in their life…, when [they]’ll need a wheelchair…, and even the day [they]’ll die, with remarkable certainty.” (This service is not yet publicly offered, however.)

Goetz distills the ethos of PatientsLikeMe as “an experiment in the future of medicine, running in real time.” And it is not the only such experiment: another one is 23andMe, a “personal genomics” company which, for US$999, will answer the questions: “Where do I come from? What are my roots?” and “How do I compare to other people?” It does so by analyzing a saliva sample for some 600,000 genetic variations linked to disease and other factors such as ancestry, height, and eye color. Customers can then compare their genomic profile, disease propensity, haplotype, and ancestry online with those of other customers, who may be family members, friends, celebrities, or total strangers.

The company’s ultimate goal is a genomic database large enough to reveal scientifically and medically relevant information about its users, who can opt to provide a detailed medical history and have their genomic and phenotypic data used in research. 23andMe hopes to spark grassroots, community-driven genomics research into disease. The fact that genomics pioneer George Church is a member of 23andMe’s scientific advisory board speaks to its credibility.

Weight Control and the Mouse Model

Speaking of models and experiments: Experimental mice were able to eat hearty meals while gaining less weight than normal mice on the same diet. Scientists had removed an enzyme from the fat cells of the experimental mice, which increased their metabolism so they burned up more fat and sugars. While there is healthy skepticism that these results in mice could translate to diabetes-inhibiting weight-loss pills for humans, research such as this keeps building and it won’t stop until we get to where the mice are at.

However, and fortunately for experimental mice, we may have to get there without them. A study of 120 essential genes (necessary for reproduction) present and identical in both mice and humans showed that 22 percent of them were not, in fact, essential in mice. This begins to explain something already observed: that inferences about human gene function drawn from the mouse model may not always be right, and that a primate model (closer to the human reproductive phenotype) would be better. In our view, an in silico, mathematical, systems biology model would be better still, and will ultimately replace animal models completely. Dr. David Eddy has pioneered in this area, with his Archimedes model, and it is clear that a combination of the data and analytic engines from PatientsLikeMe and 23andMe would take us further down that road.

Potpourri

Patient self-care, grassroots medical and genomics research, and in silico biology are tremors contributing to the HealthQuake. Here is a potpourri of other tremors reported in recent months:

Plastic Surge

While the number of plastic surgery procedures performed in the US is rising (by 7 percent in 2006, to almost 11 million; mainly breast augmentation and nose reshaping), the social stigma attached to cosmetic surgery is falling, according to a New York Times article. Both trends are a part of the bigger trend to superhealth – the acquisition of a physique better than Nature can endow.

Another example of the trend is a prototype contact lens containing electronic circuitry and LEDs enabling it to produce images superimposed on the wearer’s vision. Possible uses include heads-up information displays for drivers or pilots, virtual world and videogame environments, and Web browsing. A version that has a basic display with just a few pixels could be ready for human tests “fairly quickly.”

Hacking into Cyborgs

Computer security researchers have succeeded in gaining wireless access to a combination heart defibrillator and pacemaker in the lab. They were then able to gather personal patient data stored in the device, shut it down, or deliver jolts of electricity sufficient to kill an actual implant patient. It took extreme sophistication and expensive equipment, making it unlikely that your average mutant Ninja teenager will be hacking into patients any time soon.

But with implants increasingly being designed to connect wirelessly to the Internet, so doctors can monitor patients remotely, the risk of hacking will grow. The US Food and Drug Administration has increased its scrutiny of radio devices in implants, but more to prevent unintentional than deliberate interference.

Evidence-Based Medicine Adopted

The 30-year rise of angioplasty has ended and appears to have declined (in the US) by 10-15 percent over the past two years, as a result of research evidence suggesting that the procedure is overused and its modest benefits often not worth the high cost. This illustrates that the adoption of evidence-based medicine is reducing the time it takes to get research findings to where they matter: the patient’s bedside. For example, the use of drug-coated stents in angioplasty procedures fell almost in half when news broke that they can promote clots, while the use of medical therapies such as aggressive treatment with statins rose quickly after studies showing their effectiveness. It seems that doctors can keep up with the tsunami of medical innovation, at least if the news is big enough.

Trouble at t’ Pharm

The US pharmaceutical industry appears to be in for a rough ride. Political support for importing less-expensive drugs into the US from Canada, for allowing Medicare to negotiate drug prices, and for allowing the US Food and Drug Administration to approve generic versions of biotech drugs all put pressure on pricing. The industry’s marketing, research, and information-disclosure practices are under attack in Congress. A flood of public scandals about drugs that don’t work as advertised and/or have been improperly evaluated doesn’t help the image. Add to all this the accelerating death of the blockbuster drug at the hands of pharmacogenomics, and Big Pharma seems to be in for big trouble.

The Proton Beam Pitfall

The question whether proton beam therapy is more effective in treating prostate and other common cancers is as far from settled as the cost of the machines – currently US$150 million plus, all told. The reported development of several less costly machines could leave hospitals that pay today’s going rate with red faces and red ink.

The Congressional Budget Office recently estimated that technological advances accounted for about half the growth in healthcare spending in the past several decades, but may not have been worth the cost.

Pet Cloning Business

In February a company created by the Seoul National University researchers who first cloned a dog in 2005 began taking orders for the cloning of pet dogs, at US$150,000 per pooch.

India-Africa Telemedicine

Several hospitals in Ethiopia and India have become linked by a fiber-optic Internet intercontinental telemedicine connection as part of an effort to provide healthcare access to grossly underserved parts of Africa. India plans to fund several such projects and train Africans for five years before handing the scheme over to African countries.

Synthetic Life

Late last year, researchers engineered an entire set of genetic instructions needed to drive a bacterial cell. Their work makes possible the creation of synthetic living organisms that could be engineered to produce clean fuels or take carbon dioxide out of the atmosphere, for example.

One commentator stressed the need to understand what effect altering the DNA sequence of an organism would have upon its behavior. Another said he “would be surprised if by 2012 it were not technically possible to routinely design and construct the genomes of any bacteria or single celled eukaryote, which also means that it will be possible to construct some mammalian chromosomes.”

All this is happening in a regulatory vacuum, with “science delving into matters that have potentially dangerous consequences,” as one bio-ethicist put it.

AI in SL

An artificially intelligent avatar created in Second Life has a limited ability to converse and reason, but was nevertheless able successfully to make two or three inferences assessed to be at the level of a 4-year-old child. More sophisticated future versions, powered by supercomputers and with IBM’s support, may have enough intelligence to be used (for example) in training exercises for emergency situations, simulated in Second Life.